Work will continue on the study of the delayed toxicity of trialkyl phosphorothioates and phosphorodithioates, and dialkyl alkyl- and arylphosphonothioates. Structure-activity studies will focus on a series of S-alkyl O,O-dimethyl and O,O-diethyl phosphorothioates, O,S-dialkyl alkyl- and arylphosphonothioates in relation to acute and delayed toxicity to rats, and in vivo and in vitro inhibition of different esterases, including true and pseudo cholinesterase. The effect of atropine and 2-PAM on the toxicity of these compounds will be examined. The effect of chirality of the phosphorous atom on rat toxicity of these compounds will also be examined. Studies on the mode of action of O,O,S-trimethyl phosphorothioate will continue with (CH3O-14C) compound. Metabolism and pharmacokinetic studies are in progress to determine the nature and distribution of metabolic products in different tissues, and in urine, feces and blood. The effect of the antagonist, O,O,O-trimethyl phosphorothioate, on the metabolism and pharmacokinetics of 14C-O,O,S-trimethyl phosphorothioate will also be examined following oral and intraperitoneal administration and by administration via the cannulated exterior jugular vein. Work will continue on the inhibition of different kinds of esterases by O,O,S-trimethyl phosphorothioate and the effect of the O,O,O-trimethyl isomer on inhibition.